Figure 8. The proposed effects of ageing on eNOS uncoupling.

BH₄ content is reduced in soleus muscle arterioles of aged rats. With limited availability of BH₄, eNOS becomes uncoupled and leads to generation of O₂⁻ rather than NO. Peroxynitrite (ONOO⁻), a product of NO and O₂⁻ generated through eNOS uncoupling, NADPH oxidases and other sources, could further reduce BH₄ availability. Vascular SOD scavenges O₂⁻, which can produce the vasodilator H₂O₂. In the presence of catalytic transition metals (i.e. Fe²⁺), H₂O₂ can produce the potent vasoconstrictor OH⁻. H₂O₂ is converted to H₂O and O₂ in the presence of catalase.